Cytokinetics Publication in Cancer Research Demonstrates Antitumor Activity of a Kinesin Spindle Protein (KSP) Inhibitor in a Preclinical Model
Preclinical Proof of Concept Emerges from Company’s Research Efforts
South San Francisco, CA - May 3, 2004
Cytokinetics, Inc. (Nasdaq: CYTK) announced today the publication of detailed preclinical research findings from a study demonstrating the feasibility of small molecule inhibition of kinesin spindle protein (KSP) for the potential treatment of cancer. The article is featured in the cover sidebar of the May 2004 issue of Cancer Research, a publication of the American Association for Cancer Research, and in Cancer Research Highlights on the AACR homepage, www.aacr.org.
The study found that an inhibitor of kinesin spindle protein (KSP) exhibited anti-tumor activity comparable to or exceeding that of paclitaxel in a mouse model of cancer. The research also confirmed that in normal cells, KSP is most abundant in proliferating human tissues and absent from non-proliferating nerve cells. KSP is a cytoskeletal mitotic kinesin motor protein that plays an essential role in the formation of a key cytoskeletal structure, known as the mitotic spindle, which plays the central role in the mechanics of cell division.
“We are pleased to be able to share these data with the cancer research community,” said James H. Sabry, M.D., Ph.D., Cytokinetics’ President and Chief Executive Officer. “The results of these experiments have contributed to the in vitro and in vivo preclinical hypothesis that inhibition of KSP using a small molecule could be an effective means of treating cancer. We are currently testing this hypothesis in Phase II clinical trials with another KSP inhibitor, SB-715992 under our collaboration with GlaxoSmithKline.”
Background
Cytokinetics and GlaxoSmithKline (GSK) established a strategic alliance in June 2001 to discover, develop and commercialize small molecule therapeutics that target mitotic kinesins for the treatment of cancer and other diseases. In January 2004, Cytokinetics announced that GSK initiated a broad Phase II clinical trials program designed to evaluate the effectiveness of SB-715992, a small molecule inhibitor of KSP, in the treatment of many different types of cancer. In addition, GSK is expecting to initiate Phase I clinical trials in early 2004 for SB-743921, a second KSP inhibitor, that is designed to investigate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of this drug candidate in patients with advanced cancers.
Since their introduction over 30 years ago, anti-mitotic drugs (taxanes and vinca alkaloids) have advanced the treatment of cancer and are commonly used for the treatment of several tumor types. However, these drugs have demonstrated no treatment benefit against certain tumor types. In addition, these drugs target tubulin, a cytoskeletal protein involved not only in mitosis and cell proliferation, but also in other important cellular functions. The inhibition of these other cellular functions produces dose-limiting toxicities such as peripheral neuropathy, an impairment of the peripheral nervous system. Neuropathies result when these drugs interfere with the dynamics of microtubule filaments that are responsible for the long-distance transport of important cellular components within nerve cells.
Cytokinetics’ cancer drug candidates, SB-715992 and SB-743921, are structurally distinct small molecule compounds that modulate cell proliferation and promote cancer cell death by specifically inhibiting KSP. KSP is a mitotic kinesin that is essential for cell proliferation, a process which when unregulated, results in tumor growth. Mitotic kinesins are essential to mitosis, and, unlike tubulin, appear to have no role in unrelated cellular functions. Drugs that inhibit KSP and other mitotic kinesins may represent the next generation of anti-mitotic cancer drugs by arresting mitosis and cell proliferation without impacting unrelated, normal cellular functions, avoiding many of the toxicities commonly experienced by patients treated with existing anti-mitotic drugs.
About Cytokinetics
Cytokinetics is a leading biopharmaceutical company focused on the discovery, development and commercialization of novel small molecule drugs that specifically target the cytoskeleton. The cytoskeleton is a complex biological infrastructure that plays a fundamental role within every human cell. Cytokinetics’ focus on the cytoskeleton enables it to develop novel and potentially safer and more effective classes of drugs directed at treatments for cancer, cardiovascular disease, fungal diseases and other diseases. Cytokinetics has developed a cell biology driven approach and proprietary technologies to evaluate the function of many interacting proteins in the complex environment of the intact human cell. Cytokinetics employs the PUMA™ system and Cytometrix™ technologies to enable early identification and automated prioritization of compounds that are highly selective for their intended protein targets without other cellular effects, and are thereby less likely to give rise to clinical side effects. Cytokinetics and GlaxoSmithKline have entered into a strategic alliance to discover, develop and commercialize small molecule therapeutics targeting human mitotic kinesins for applications in the treatment of cancer and other diseases. GlaxoSmithKline is conducting Phase II clinical trials with SB-715992 and is expecting to initiate Phase I clinical trials in early 2004 for SB-743921, each a drug candidate that has emerged from the strategic alliance. Additional information about Cytokinetics can be obtained at www.cytokinetics.com.
This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 and it is the Company’s intent that such statements be protected by the safe harbor created thereby. Examples of such statements include, but are not limited to, statements relating to the potential benefits of the Company’s drug candidates. Such statements are based on management’s current expectations, but actual results may differ materially due to various factors. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, testing, regulatory approval, production and marketing of the Company’s drug candidates that could slow or prevent product approval or market acceptance (including the risk that uncertainty of patent protection for the Company’s intellectual property or trade secrets, the Company’s ability to obtain additional financing if necessary and unanticipated research and development and other costs). For further information regarding these and other risks related to the Company’s business, investors should consult the Company’s filings with the Securities and Exchange Commission. Cytokinetics does not undertake any obligation to update forward-looking statements.
